Neurotransmission

Electricity

• Electrical currents are flows of charged particles (here electrons).
• Like charges repel, opposite charges attract.
• Currents only flow through materials that conduct electricity.
• Voltage is a measure of how much potential there is for charge to move – how much stored electrical energy (like water pressure).

Ohms Law: Current = Potential/Resistance

Conduction in nerves is different to wires
• Hermann von Helmholtz (1849) – measured speed of nerve conduction by stimulating frog sciatic nerve and measuring time to constrict muscle.
• Nerve conduction ~ 30-40 m/s, 1 million times slower than electricity flows down a wire

How do cells signal electrically?

·        Movement of ions

·        Electrically charged particles (Na+ and Cl –)

·        Some ions flow at rest

·        ***

Cell Membrane

·        Cells surrounded by a lipid membrane

·        Water soluble things can’t pass through

Concentration Gradients

Outside:

·        Na+

·        Cl –

·        Ca2+

Inside:

·        Proteins

·        K+

There are ion channels through the membrane..

There is also an electrical gradient (from a high concentration outside to a low concentration inside)

Equilibrium potentials

Potential across membrane at which there is no net flow of an ion

Equilibrium potential dictated by concentration difference and ion charge.

Membrane potential

Set by electrochemical gradient and permeability of membrane to different ions. Equilibrium is ~70mV. The resting membrane potential of neurons is near to equilibrium potential for potassium.

Sodium Potassium pumps maintain ion gradients

Neuron Components

Electrical Signals

·        Can be measured with a voltmeter.

·        Resting membrane potential is negative

·         Action potential – wave of transient depolarisation that travels down the axon.

·        Fast (compared to chemical signals)

Changing Membrane Permeability – Ion channels
• Holes in the membrane that allow ions to enter and leave the cell.
• Are selective for different ions
• Can be open all the time (e.g. K+ leak channels that set the resting membrane
potential)
• Others are opened by different stimuli – e.g. a change in voltage, binding specific molecules
• Ions flow down electrical and chemical (concentration) gradients

Action potential is generated by opening and closing ion channels

·        Wave of transient depolarisation of cell membrane

·        Conveys a fast signal from one place to another place in the body

·        It is generated by changes in membrane permeability due to opening and closing of voltage gated ions.

Action Potential

is a self-regenerating electrical wave
• is a transient change (~1ms) in membrane potential.
• occurs only if a threshold membrane potential is achieved in the axon initial segment (axon hillock), which transiently opens voltage gated sodium channels.

Action Potential Process

1)     Threshold potential reached

2) Depolarisation due to opening of sodium channels
3) Repolarisation due to inactivation of sodium channels and opening of voltage-gated potassium channels
4) Hyperpolarisation as voltage-gated potassium channels are still open.
5) Sodium channels released from inactivation (can fire AP again)

Refractory Periods

When all sodium channels are inactivated there is an absolute refractory period where no more action potentials can be formed.

Relative refractory period = where some channels are inactivated and can only be reopened by strong stimuli.

Action potentials are all or nothing.

Action potentials transmit along axons. As it moves it depolarises the next segment of membrane and opens sodium channels. If not enough sodium channels are opened, membrane potential reaches threshold potential and action potential propagates. The area that just generated an action potential cannot fire another Na+ Sodium channel as it is now inactivated

Speed

Action potential speed: 0.1m/s à 100 m/s

This depends on:

·        How fast membrane potential changes due to:

-        resistance of membrane (slower of charge can leak out)

-        Capacitance of cell (how easy it is to change membrane voltage

·        How far depolarisations can spread along the axon due to

-        Membrane resistance

-        Diameter (faster if larger

Myelination

Myelin insulates the membrane which means less charge is lost. So the charge can spread further. Saltatory Conduction = Where action potentials travel from one node of Ranvier to the other. It is faster and efficient as less ions flow so less ATP is needed to pump them back.

Presynaptic Cell

1.      Action potential arrives

2.      Membrane depolarisation opens voltage-gated calcium channels

3.      Calcium inside cells cause vesicles of neurotransmitter to fuse with membrane

4.      Neurotransmitter diffuses through synaptic cleft.

Postsynaptic cell

5.      Neurotransmitter binds to ligand (molecule) gated ion channel.

6.      Ions flow through the channel, either depolarising or hyperpolarising the post-synaptic membrane

Glutamate Receptors

Depolarisation of dendrites by ion flow through GLUTAMATE receptors generates an excitatory post-synaptic potential. This drives membrane potential towards the threshold for action potential firing.

NMDA receptor. These are ion channels that bind glutamate and be depolarised to be opened. They also let calcium in which causes changes in synapse to make it better or worse.

Metabotropic Glutamate receptors – bind glutamate and trigger intracellular signalling.

Summation

Summation is needed to generate an action potential as a single potential is not enough. Many action potentials over time can reach the threshold (temporal summation) . Also different synapses can add potentials together to generate an AP. (spatial summation)

Inhibition

GABA is the main inhibitory neurotransmitter in the brain. It opens chloride channels allowing negative charge to generate an inhibitory post-synaptic potential, making it harder to repolarise the membrane. So it is harder for another action potential to form.

Synaptic Integration = summation of excitatory and inhibitory inputs. Strength of input relates to distance of synapse from axon hillock, which is affected by surface area of the neuron.

Soma = integrates of excitatory and inhibitory synapses decide whether to fire an action potential

Larger and longer stimuli can cause more frequent firing of action porential

Neuronal Networks = How neurons are wired together affects computations they perform and the information they represent.

Lateral inhibition.